We investigated the humoral and cellular responses of ovarian cancer patients treated with viral oncolysates (VO) tumor vaccines. All patients treated with VO developed tumor cell surface-reacting antibodies and anti-hemagglutinin antibodies. Furthermore, PBMC from these patients developed cellular proliferative responses to the cellular oncolysates (CO). The in vitro proliferating population consisted mainly of CD4+ cells, as demonstrated by depletion experiments using the corresponding monoclonal antibodies and complement and by examination of the phenotype of the cells stimulated in culture with VO or cellular oncolysates. Furthermore, in the patients treated with VO we observed an increased helper activity to immunoglobulin production by PBMC collected post-VO treatment in the PWM-driven differentiation system. The helper activity was much higher in patients treated with IL-2 plus VO than IL-2 alone.